Predicting Binding Affinities for GPCR Ligands Using Free-Energy Perturbation.

ABSTRACT: The rapid growth of structural information for G-protein-coupled receptors (GPCRs) has led to a greater understanding of their structure, function, selectivity, and ligand binding. Although novel ligands have been identified using methods such as virtual screening, computationally driven lead optimization has been possible only in isolated cases because of challenges associated with predicting binding free energies for related compounds. Here, we provide a systematic characterization of the performance of free-energy perturbation (FEP) calculations to predict relative binding free energies of congeneric ligands binding to GPCR targets using a consistent protocol and no adjustable parameters. Using the FEP+ package, first we validated the protocol, which includes a full lipid bilayer and ex

SUBMITTER: Lenselink EB 

PROVIDER: S-EPMC6044636 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature